{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:39:23Z","timestamp":1791049163368,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["RC 16\/2019"],"award-info":[{"award-number":["RC 16\/2019"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>Ketamine provides the highest safety profile among sedatives for procedural sedation and analgesia in the pediatric emergency setting. However, it can cause vomiting and recovery agitation. No studies have examined epigenetic factors, such as microRNAs, for predicting the occurrence of these adverse events. Neuronal\u2010derived extracellular vesicle microRNA profiles were studied to predict the occurrence of ketamine\u2010induced vomiting and recovery agitation in children. For this aim, a single\u2010center prospective pharmacoepigenetic study was performed and 50 children who underwent procedural sedation with intravenous ketamine as the only sedative drug were enrolled between October 2019 and November 2022. MiRNA profiling in plasma neural\u2010derived extracellular vesicles was analyzed through next\u2010generation sequencing and measured before treatment with ketamine. Twenty\u2010two patients experienced vomiting or recovery agitation. Among the 16 differentially expressed microRNAs, the upregulated miR\u201015a\u20105p and miR\u2010484 targeted genes related to N\u2010methyl\u2010D\u2010aspartate (NMDA) receptor activity, including glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A). Preliminary data confirmed lower GRIN2A levels in patients who developed these events. Downregulated miR\u2010126\u20103p and miR\u201024\u20103p targeted AMPA receptor\u2010associated genes. Functional analyses of gene targets revealed the enrichment of glutamatergic and neurotrophins signaling. Recovery agitation was associated with this network. Vomiting was related to dopaminergic and cholinergic systems. Three miRNAs (miR\u201018a\u20103p, miR\u2010484, and miR\u2010548az\u20105p) were identified as predictive biomarkers (AUC 0.814; 95% CI: 0.632\u20130.956) for ketamine\u2010induced vomiting and recovery agitation. MicroRNA profiles can predict the development of ketamine\u2010induced vomiting or recovery agitation in children. This study contributes to the understanding of the mechanisms underlying ketamine\u2010induced adverse events.<\/jats:p>","DOI":"10.1002\/cpt.3420","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T02:15:33Z","timestamp":1724292933000},"page":"174-183","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Neuron\u2010Derived Extracellular Vesicles miRNA Profiles Identify Children Who Experience Adverse Events after Ketamine Administration for Procedural Sedation"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1355-3782","authenticated-orcid":false,"given":"Marianna","family":"Lucaf\u00f2","sequence":"first","affiliation":[{"name":"Department of Life Sciences University of Trieste  Trieste Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5756-4750","authenticated-orcid":false,"given":"Carlotta","family":"Bidoli","sequence":"additional","affiliation":[{"name":"Department of Life Sciences University of Trieste  Trieste Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1304-6190","authenticated-orcid":false,"given":"Martina","family":"Franzin","sequence":"additional","affiliation":[{"name":"Department of Advanced Translational Diagnostics Institute for Maternal and Child Health IRCCS \u201cBurlo Garofolo\u201d  Trieste Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6908-8352","authenticated-orcid":false,"given":"Erez","family":"Eitan","sequence":"additional","affiliation":[{"name":"NeuroDex Inc.  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